Dynamic imaging reveals that brain-derived neurotrophic factor can independently regulate motility and direction of neuroblasts within the rostral migratory stream
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Abstract
Neuronal precursors generated in the subventricular zone (SVZ) migrate through the
rostral migratory stream (RMS) to the olfactory bulb (OB). Although, the mechanisms
regulating this migration remain largely unknown. Studies have shown that molecular
factors, such as brain-derived neurotrophic factor (BDNF) emanating from the OB, may
function as chemoattractants drawing neuroblasts toward their target. To better understand
the role of BDNF in RMS migration, we used an acute slice preparation from early postnatal
mice to track the tangential migration of GAD65-GFP labeled RMS neuroblasts with confocal
time-lapse imaging. By quantifying the cell dynamics using specific directional and
motility criteria, our results showed that removal of the OB did not alter the overall
directional trajectory of neuroblasts, but did reduce their motility. This suggested
that additional guidance factors present locally within the RMS region also contribute
to this migration. Here we report that BDNF and its high affinity receptor, tyrosine
kinase receptor type 2 (TrkB), are indeed heterogeneously expressed within the RMS
at postnatal day 7. By altering BDNF levels within the entire pathway, we showed that
reduced BDNF signaling changes both neuroblast motility and direction, while increased
BDNF levels changes only motility. Together these data reveal that during this early
postnatal period BDNF plays a complex role in regulating both the motility and direction
of RMS flow, and that BDNF comes from sources within the RMS itself, as well as from
the olfactory bulb.
Published by Elsevier Ltd.